Polyxena of Hesse-Rheinfels-Rotenburg (Polyxena Christina Johanna; 21 September 1706 – 13 January 1735) was the second wife of Charles Emmanuel, Prince of Piedmont, future King Charles Emmanuel III of Sardinia.

The engagement was announced on 2 July 1724. The marriage was celebrated in person at Thonon in Chablais on 20 August 1724. The happy marriage produced six children.

Praised as an attractive, cultured and kind woman, Polyxena founded a home for penniless mothers in Turin in 1732, redecorated the Villa della Regina, the hunting lodge of Stupingi, and the Church of Saint Giuseppe in Turin. She popularised chinoiserie. She was also a patron of Giovanni Battista Crosato, a baroque painter.